Cytogenetic analysis of cells from lymphomatous tissue is becoming a valuable tool in the understanding and subclassification of non-Hodgkin's lymphoma. Yet the standard techniques utilized for the visualization of chromosomes from lymphoma cells are often not adequate for detailed analysis, and chromosomal abnormalities can be overlooked with the relatively few and contracted metaphases obtained (320-150 bands per haploid set). With these techniques, less than 70 percent of all patients can be successfully analyzed and often it is not possible to fully characterize the structual chromosomal defects found in a large number of patients. Although several nonrandom chromosomal changes have been noted in past reports of isolated cases, the use of different histologic classifications and meager description of patients has made it difficult to link a specific chromosomal defect with a distinct lymphoma subgroup. With the amethoterin cell synchronization technique developed in this laboratory, a relatively large number of cells in prometaphase (850 band stage), early metaphase (550 band stage) and elogated mid-metaphase (400 band stage) are routinely obtained. Technical improvements brought about by this high-resolution chromosome technique have shown that all cases thus far studied with non-Hodgkin's non-Burk-itt's lymphoma can be analyzed in detail, have abnormal karyotypes (24 out of 24 cases), and subgroups with specific chromosomal defects are found. This work is further facilitated by the use of the new international histologic classification of non-Hodgkin's lymphoma and recent advances in the study of surface and cytoplasmic lymphoid cell markers. This approach, together with the ususually large number of patients we have available for study (410 in 3 years) gives us the unique opportunity to provide vital information to the understanding of the biology, complexity, and prognosis of these disorders. Recently, we have developed a G-banded late and mid-prophase method to obtain 1200 to 2000 bands per haploid set. Since the human genome is believed to contain only some 30,000 genes, the application of this technique to the study of lymphomas should provide and unprecented level of sophistication in cancer cytogenetics. Our method would make it possible to the precise breakpoints involved in the specific reciprocal translocations found in various, neoplasias, postulated to involve specific "cancer gen" sites.